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FATAL PNEUMONIA AFTER GLANDULAR FEVER AND RUBELLA
1210 volatilisation and subsequent release into the atmosphere of about ten times more anaesthetic than is required to anaesthetise the patient. Such wastage and the resulting pollution does not seem reasonable. Department of Anaesthetics, Aberdeen Royal Infirmary
R. C. RODGERS
Department of Environmental and Occupational Medicine, University of Aberdeen,
J. A. S. ROSS
Aberdeen AB9 2ZD
PHENYTOIN AND FASTING
SIR,-Dr Aslam and J. V. Wilson (April 29, p 955) imply that the phenytoin during the day had precipitated a seizure in a fasting patient with previously well-controlled epilepsy, even though the patient continued to take a third of his dose at night. The explanation is unlikely. The plasma half-life of phenytoin after acute administration in adults is about 15 h. However, with chronic administration, the half-life exceeds 4 days (presumably due to saturation of the hepatic hydroxylation reaction and/or inhibition of drug elimination by metabolites). In other words, after a few days’ treatment, the phenytoin decay curve follows zero-order kinetics. Chronically treated but well-controlled epileptic patients usually have seizures omission of
when their plasma phenytoin levels fall below 10 JlgjmJ.1 It is unlikely that this patient’s phenytoin level had fallen to the critical value in such a short time, especially as the patient had merely reduced the dose. This patient’s isolated epileptic attack was probably coincidental with his dose reduction. Another possibility is mild hypoglycaemia during the fast, which can lower the threshold and precipitate seizures in some well-controlled epileptic patients. This group of patients should be identified and advised accordingly. It could be argued that there is no advantage to be gained by dividing the daily dose of phenytoin (except perhaps for better tolerance in some patients) and, therefore, patients who prefer to take a single or nocturnal dose of the drug should be encouraged to do so. Glasgow University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF 1. Richens A. Clinical
A. M. O. BAKHEIT
pharmacokinetics of phenytoin. Clin Pharmacokinet 1979;
4:
153-69.
FATAL PNEUMONIA AFTER GLANDULAR FEVER AND RUBELLA
SIR,-An 11-year-old boy previously in good health was seen by general practitioner on Feb 3, 1987, with a morbiliform rash, enlarged lymph nodes, and a mild sore throat. Although the rash had cleared and the glands were no longer palpable two days later both elbows were hot and painful. By the next day the elbows were normal but the patient was delirious and had minimal signs in his left chest. He was coughing and was admitted. The patient was breathing fast with chest pain, temperature was 39°C, and pulse
his
100-120/min
with normal blood pressure. Mouth ulcers had
developed in the past two days. The boy had striking bronchial breathing in the left lower and middle zones, cold extremities with a dusky hue, petechiae on the palate, and extensive mouth ulcers. Anterior and posterior cervical glands were palpable. On Feb 4 haemoglobin was 13-7 g/dl and white cell count was 7-6 x 109/1 with a normal differential count. X-ray showed generalised consolidation and probable pulmonary oedema. The QT interval was possibly long on electrocardiogram. Blood pH was 7-4, pC02 53 kPa, and p02 37 kPa. Pulmonary oedema consequent upon myocarditis or severe mycoplasma pneumonia was diagnosed. Analgesics, frusemide, oxygen, erythromycin, and netilmicin were started. By the evening p02 was only 6-4 kPa. A brisk diuresis started in the night and by the next day the boy felt better with less chest pain. He was drinking well but was still grey (p02 4’kPa). Increasing the oxygen flow raised the p02 to 9-6 kPa and by Feb 8 he was improving. Blood, urine and sputum cultures were normal.
deteriorated on Feb 9 with bloody diarrhoea, a cardiovascular system, and signs of massive consolidation of both lung fields. He was transferred to the intensive therapy unit and intubated since p02 had dropped to 37 kPa. Haemoglobin had fallen to 98 g/dl. Penicillin and steroids were started. On Feb 10 blood pressure dropped and the patient died. Necropsy revealed widespread pneumonia. There were no virus inclusions and stains for bacteria and P carinii were negative. Sera taken on Feb 9 and 11 were positive for rubella-specific IgM. Serological examination for other viruses and bacteria was negative. The Paul Bunnell test was negative and no virus was cultured from the throat or tongue; nor was a mycoplasma cultured post-mortem from blood or peritoneal fluid. No virus could be demonstrated by immunofluoresence or culture from lung tissue. Examination of the serum specimens at the Bristol Public Health Laboratory revealed antibody to Epstein-Barr virus capsid antigen (titre 256) and no antibody to the nuclear antigen. This suggested that the boy had recently had glandular fever and that the consequent immunosuppression might have enhanced the pathogenicity of the rubella virus infection. It is also possible that the concurrent rubella infection enhanced the pathogenicity of the Epstein-Barr virus infection. However, we cannot establish in what order these infections occurred. The
patient hyperdynamic
J. V. S. PETHER Public Health Laboratory Service, Kingsdown, Bristol BS2 8EL
E. OWEN CAUL T. J. BETTERIDGE K. T. NICHOLSON
FALSE POSITIVITY WITH ONE-STEP AND CONVENTIONAL ELISA FOR ALPHA-FETOPROTEIN INSEMINOMA
SIR,-We present two cases that support Dahlmann and Hartlapp’s observation1 of a false-positive result in a one-step monoclonal assay for alpha-fetoprotein (AFP). Case 1 (M/50).-Cavemous tuberculosis and operative treatment for right-sided strangulated inguinal hernia in 1983, during which seminoma testis was found and semi-castration was done. Regional lymphangiography was not done. The patient has received radiation therapy since January, 1984. Postoperative AFP concentration was 11 ng/ml (radioimmunoassay [RIA], Serono; normal value below 15 ngjml).2 AFP in serum samples taken in May, 1985, measured by sandwich ELISA, was 89 ng/ml. Repeat RIA showed AFP concentration of 10 ng/ml. Case 2 (M/34).-Right-sided semi-castration and regional lymphangiography were done in December, 1983. Histological findings confirmed seminoma; no metastases were found in lymph nodes. The patient received postoperative radiation therapy. AFP concentration in blood taken five days after operation was below 5 ng/ml (RIA). Until May, 1985, routine investigation every three months showed an AFP concentration of below 8 ng/ml. In May, 1985 AFP concentration by ELISA was greater than 200 ng/ml. Repeat investigation by RIA gave a value of 8 ng/ml. The concentration of human &bgr;-chorionic gonadotropin (RIA, Amersham) was normal and no clinical signs of activation were found; so no treatment was given to date (March, 1989), AFP concentration was over 1000 ng/ml by ELISA but below 8 ng/ml by RIA. We have developed a one-step ELISA for AFP and we have been using it since March, 1986.3 With this assay, we fmd the same AFP concentration as by the traditional sandwich technique. While investigating the contradiction between the RIA and ELISA methods, we assumed that the sera of these two patients contained a protein that was immunologically similar to that of AFP ("pseudo-AFP"). In the ELISA which is based on a noncompetitive principle, this protein crossreacts with the AFP antibody, while in RIA, competing for a limited number of antibody-binding sites with true AFP, it ousts the loosely binding "pseudo-AFP". This hypothesis has been confirmed by Dahhnann and Hartlapp. The Waaler-Rose reaction gave a positive result in both our patients despite the fact that neither showed signs of rheumatoid
R. C. RODGERS
Department of Environmental and Occupational Medicine, University of Aberdeen,
J. A. S. ROSS
Aberdeen AB9 2ZD
PHENYTOIN AND FASTING
SIR,-Dr Aslam and J. V. Wilson (April 29, p 955) imply that the phenytoin during the day had precipitated a seizure in a fasting patient with previously well-controlled epilepsy, even though the patient continued to take a third of his dose at night. The explanation is unlikely. The plasma half-life of phenytoin after acute administration in adults is about 15 h. However, with chronic administration, the half-life exceeds 4 days (presumably due to saturation of the hepatic hydroxylation reaction and/or inhibition of drug elimination by metabolites). In other words, after a few days’ treatment, the phenytoin decay curve follows zero-order kinetics. Chronically treated but well-controlled epileptic patients usually have seizures omission of
when their plasma phenytoin levels fall below 10 JlgjmJ.1 It is unlikely that this patient’s phenytoin level had fallen to the critical value in such a short time, especially as the patient had merely reduced the dose. This patient’s isolated epileptic attack was probably coincidental with his dose reduction. Another possibility is mild hypoglycaemia during the fast, which can lower the threshold and precipitate seizures in some well-controlled epileptic patients. This group of patients should be identified and advised accordingly. It could be argued that there is no advantage to be gained by dividing the daily dose of phenytoin (except perhaps for better tolerance in some patients) and, therefore, patients who prefer to take a single or nocturnal dose of the drug should be encouraged to do so. Glasgow University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF 1. Richens A. Clinical
A. M. O. BAKHEIT
pharmacokinetics of phenytoin. Clin Pharmacokinet 1979;
4:
153-69.
FATAL PNEUMONIA AFTER GLANDULAR FEVER AND RUBELLA
SIR,-An 11-year-old boy previously in good health was seen by general practitioner on Feb 3, 1987, with a morbiliform rash, enlarged lymph nodes, and a mild sore throat. Although the rash had cleared and the glands were no longer palpable two days later both elbows were hot and painful. By the next day the elbows were normal but the patient was delirious and had minimal signs in his left chest. He was coughing and was admitted. The patient was breathing fast with chest pain, temperature was 39°C, and pulse
his
100-120/min
with normal blood pressure. Mouth ulcers had
developed in the past two days. The boy had striking bronchial breathing in the left lower and middle zones, cold extremities with a dusky hue, petechiae on the palate, and extensive mouth ulcers. Anterior and posterior cervical glands were palpable. On Feb 4 haemoglobin was 13-7 g/dl and white cell count was 7-6 x 109/1 with a normal differential count. X-ray showed generalised consolidation and probable pulmonary oedema. The QT interval was possibly long on electrocardiogram. Blood pH was 7-4, pC02 53 kPa, and p02 37 kPa. Pulmonary oedema consequent upon myocarditis or severe mycoplasma pneumonia was diagnosed. Analgesics, frusemide, oxygen, erythromycin, and netilmicin were started. By the evening p02 was only 6-4 kPa. A brisk diuresis started in the night and by the next day the boy felt better with less chest pain. He was drinking well but was still grey (p02 4’kPa). Increasing the oxygen flow raised the p02 to 9-6 kPa and by Feb 8 he was improving. Blood, urine and sputum cultures were normal.
deteriorated on Feb 9 with bloody diarrhoea, a cardiovascular system, and signs of massive consolidation of both lung fields. He was transferred to the intensive therapy unit and intubated since p02 had dropped to 37 kPa. Haemoglobin had fallen to 98 g/dl. Penicillin and steroids were started. On Feb 10 blood pressure dropped and the patient died. Necropsy revealed widespread pneumonia. There were no virus inclusions and stains for bacteria and P carinii were negative. Sera taken on Feb 9 and 11 were positive for rubella-specific IgM. Serological examination for other viruses and bacteria was negative. The Paul Bunnell test was negative and no virus was cultured from the throat or tongue; nor was a mycoplasma cultured post-mortem from blood or peritoneal fluid. No virus could be demonstrated by immunofluoresence or culture from lung tissue. Examination of the serum specimens at the Bristol Public Health Laboratory revealed antibody to Epstein-Barr virus capsid antigen (titre 256) and no antibody to the nuclear antigen. This suggested that the boy had recently had glandular fever and that the consequent immunosuppression might have enhanced the pathogenicity of the rubella virus infection. It is also possible that the concurrent rubella infection enhanced the pathogenicity of the Epstein-Barr virus infection. However, we cannot establish in what order these infections occurred. The
patient hyperdynamic
J. V. S. PETHER Public Health Laboratory Service, Kingsdown, Bristol BS2 8EL
E. OWEN CAUL T. J. BETTERIDGE K. T. NICHOLSON
FALSE POSITIVITY WITH ONE-STEP AND CONVENTIONAL ELISA FOR ALPHA-FETOPROTEIN INSEMINOMA
SIR,-We present two cases that support Dahlmann and Hartlapp’s observation1 of a false-positive result in a one-step monoclonal assay for alpha-fetoprotein (AFP). Case 1 (M/50).-Cavemous tuberculosis and operative treatment for right-sided strangulated inguinal hernia in 1983, during which seminoma testis was found and semi-castration was done. Regional lymphangiography was not done. The patient has received radiation therapy since January, 1984. Postoperative AFP concentration was 11 ng/ml (radioimmunoassay [RIA], Serono; normal value below 15 ngjml).2 AFP in serum samples taken in May, 1985, measured by sandwich ELISA, was 89 ng/ml. Repeat RIA showed AFP concentration of 10 ng/ml. Case 2 (M/34).-Right-sided semi-castration and regional lymphangiography were done in December, 1983. Histological findings confirmed seminoma; no metastases were found in lymph nodes. The patient received postoperative radiation therapy. AFP concentration in blood taken five days after operation was below 5 ng/ml (RIA). Until May, 1985, routine investigation every three months showed an AFP concentration of below 8 ng/ml. In May, 1985 AFP concentration by ELISA was greater than 200 ng/ml. Repeat investigation by RIA gave a value of 8 ng/ml. The concentration of human &bgr;-chorionic gonadotropin (RIA, Amersham) was normal and no clinical signs of activation were found; so no treatment was given to date (March, 1989), AFP concentration was over 1000 ng/ml by ELISA but below 8 ng/ml by RIA. We have developed a one-step ELISA for AFP and we have been using it since March, 1986.3 With this assay, we fmd the same AFP concentration as by the traditional sandwich technique. While investigating the contradiction between the RIA and ELISA methods, we assumed that the sera of these two patients contained a protein that was immunologically similar to that of AFP ("pseudo-AFP"). In the ELISA which is based on a noncompetitive principle, this protein crossreacts with the AFP antibody, while in RIA, competing for a limited number of antibody-binding sites with true AFP, it ousts the loosely binding "pseudo-AFP". This hypothesis has been confirmed by Dahhnann and Hartlapp. The Waaler-Rose reaction gave a positive result in both our patients despite the fact that neither showed signs of rheumatoid